scholarly journals Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in Aspergillus niger in Peanuts

2021 ◽  
Vol 12 ◽  
Author(s):  
Manlin Xu ◽  
Xia Zhang ◽  
Jing Yu ◽  
Zhiqing Guo ◽  
Ying Li ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Protein Interactions ◽  
Root Rot ◽  
Bioinformatics Analysis ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Functional Studies ◽  
Novel Proteins ◽  
Proteasome Subunits ◽  
Cellular Compartments

Aspergillus niger is a very destructive pathogen causing severe peanut root rot, especially in the seeding stage of peanuts (Arachis hypogaea), and often leading to the death of the plant. Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly detected post-translational modification identified in several species. In this study, we identified 5041 Khib sites on 1,453 modified proteins in A. niger. Compared with five other species, A. niger has conserved and novel proteins. Bioinformatics analysis showed that Khib proteins are widely distributed in A. niger and are involved in many biological processes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that Khib proteins were significantly enriched in many cellular compartments and pathways, such as ribosomes and proteasome subunits. A total of 223 Khib proteins were part of the PPI network, thus, suggesting that Khib proteins are associated with a large range of protein interactions and diverse pathways in the life processes of A. niger. Several identified proteins are involved in pathogenesis regulation. Our research provides the first comprehensive report of Khib and an extensive database for potential functional studies on Khib proteins in this economically important fungus.

scholarly journals Assumptions of biological measurements: important considerations when evaluating western blot data

2021 ◽  
Author(s):  
Maxwell DeNies ◽  
Allen Liu ◽  
Santiago Schnell
Keyword(s):  
Cell Signaling ◽  
Western Blotting ◽  
Protein Interactions ◽  
Data Interpretation ◽  
Biological Processes ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Western Blots ◽  
Additional Information ◽  
Experimental Variability

As technological and analytical innovations rapidly advance our ability to reveal increasingly complex biological processes, the importance of understanding the assumptions behind biological measurements and sources of uncertainty are essential for data interpretation. This is particularly important in fields such as cell signaling, as due to its importance for both homeostatic and pathogenic biological processes, a quantitative understanding of the basic mechanisms of these transient events is fundamental to drug development. While developed decades ago, western blotting remains an indispensible research tool to probe cell signaling, protein expression, and protein-protein interactions. While improvements in statistical and methodology reporting have improved data quality, understanding the basic experimental assumptions and visual inspection of western blots provides additional information that is useful when evaluating experimental conclusions. Using agonist-induced receptor post-translational modification as an example we highlight the assumptions of western blotting and showcase how clues from raw western blots can hint at experimental variability that is not captured by statistics and methods that influences quantification. The purpose of this article is not to serve as a detailed review of the technical nuances and caveats of western blotting. Instead using an example we illustrate how experimental assumptions, design, and data normalization can be identified in raw data and influence data interpretation.

Role of the BH3 (Bcl-2 homology 3) domain in the regulation of apoptosis and Bcl-2-related proteins

2000 ◽  
Vol 28 (2) ◽  
pp. 51-56 ◽  
Author(s):  
R. J. Lutz
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Protein Interactions ◽  
Death Domain ◽  
Post Translational Modification ◽  
C Elegans ◽  
Functional Studies ◽  
Decision Points ◽  
Bh3 Domain ◽  
Growth Factor Signalling

The Bcl-2 family of proteins play a prominent role in the regulation of apoptosis. From the initial identification of bcl-2 as an oncogene in follicular lymphoma through genetic studies in Caenorhabditis elegans to recent functional studies focusing on the importance of mitochondrial events in cell death signalling, the members of this protein family continue to be implicated in pivotal decision points regarding the survival of the cell. The family can be divided into two classes: those such as Bcl-2 and Bcl-xL that suppress cell death, and others, such as Bak and Bax, that appear to promote apoptosis. The Bcl-2 family is characterized by specific regions of homology termed Bcl-2 homology (BH1, BH2, BH3, BH4) domains, which are critical to the function of these proteins, including their impact on cell survival and their ability to interact with other family members and regulatory proteins. The identification of the BH3 domain as a potent mediator of cell death has led to the emergence of an additional family of pro-apoptotic proteins (such as Bad, Bik, Bid and Hrk) that share identity with Bcl-2 only within this death domain. These BH3-only proteins may be part of a regulatory network serving to integrate cell survival and death signals, an assertion that is supported by the identification of a BH3-only protein, Egl-1, as part of the central core of cell death signalling in C. elegans. While the mechanism of action of the BH3-only proteins remains unclear, recent studies on the regulation of critical protein-protein interactions and activity of Bad by phosphorylation in response to growth factor signalling suggest that the active state of BH3-only proteins may be regulated by post-translational modification. Additional modes of regulation, such as transcriptional, translational and subcellular localization, are also likely to be important.

scholarly journals Post-translationally modified residues of native human osteopontin are located in clusters: identification of 36 phosphorylation and five O-glycosylation sites and their biological implications

2005 ◽  
Vol 390 (1) ◽  
pp. 285-292 ◽  
Author(s):  
Brian Christensen ◽  
Mette S. Nielsen ◽  
Kim F. Haselmann ◽  
Torben E. Petersen ◽  
Esben S. Sørensen
Keyword(s):  
Cancer Metastasis ◽  
Bone Mineralization ◽  
Casein Kinase ◽  
Target Sequence ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Glycosylation Pattern ◽  
Functional Studies ◽  
Glycosylation Sites ◽  
Cell Mediated Immune Response

OPN (osteopontin) is an integrin-binding highly phosphorylated glycoprotein, recognized as a key molecule in a multitude of biological processes such as bone mineralization, cancer metastasis, cell-mediated immune response, inflammation and cell survival. A significant regulation of OPN function is mediated through PTM (post-translational modification). Using a combination of Edman degradation and MS analyses, we have characterized the complete phosphorylation and glycosylation pattern of native human OPN. A total of 36 phosphoresidues have been localized in the sequence of OPN. There are 29 phosphorylations (Ser8, Ser10, Ser11, Ser46, Ser47, Thr50, Ser60, Ser62, Ser65, Ser83, Ser86, Ser89, Ser92, Ser104, Ser110, Ser113, Thr169, Ser179, Ser208, Ser218, Ser238, Ser247, Ser254, Ser259, Ser264, Ser275, Ser287, Ser292 and Ser294) located in the target sequence of MGCK (mammary gland casein kinase) also known as the Golgi kinase (S/T-X-E/S(P)/D). Six phosphorylations (Ser101, Ser107, Ser175, Ser199, Ser212 and Ser251) are located in the target sequence of CKII (casein kinase II) [S-X-X-E/S(P)/D] and a single phosphorylation, Ser203, is not positioned in the motif of either MGCK or CKII. The 36 phosphoresidues represent the maximal degree of modification since variability at many sites was seen. Five threonine residues are O-glycosylated (Thr118, Thr122, Thr127, Thr131 and Thr136) and two potential sites for N-glycosylation (Asn63 and Asn90) are not occupied in human milk OPN. The phosphorylations are arranged in clusters of three to five phosphoresidues and the regions containing the glycosylations and the RGD (Arg-Gly-Asp) integrin-binding sequence are devoid of phosphorylations. Knowledge about the positions and nature of PTMs in OPN will allow a rational experimental design of functional studies aimed at understanding the structural and functional interdependences in diverse biological processes in which OPN is a key molecule.

Review of Progress in Predicting Protein Methylation Sites

2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
Author(s):  
Chunyan Ao ◽  
Shunshan Jin ◽  
Yuan Lin ◽  
Quan Zou
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcriptional Activity ◽  
Regulation Of Gene Expression ◽  
Protein Methylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Regulatory Enzymes ◽  
Lysine Residues ◽  
Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

An Integrated Prediction Method for Identifying Protein-Protein Interactions

2020 ◽  
Vol 17 (4) ◽  
pp. 271-286
Author(s):  
Chang Xu ◽  
Limin Jiang ◽  
Zehua Zhang ◽  
Xuyao Yu ◽  
Renhai Chen ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Feature Vector ◽  
Prediction Method ◽  
Feature Representation ◽  
Protein Interaction Networks ◽  
Learning Approach ◽  
Biological Processes ◽  
Integrated Learning ◽  
Protein Protein Interactions ◽  
Training Process

Background: Protein-Protein Interactions (PPIs) play a key role in various biological processes. Many methods have been developed to predict protein-protein interactions and protein interaction networks. However, many existing applications are limited, because of relying on a large number of homology proteins and interaction marks. Methods: In this paper, we propose a novel integrated learning approach (RF-Ada-DF) with the sequence-based feature representation, for identifying protein-protein interactions. Our method firstly constructs a sequence-based feature vector to represent each pair of proteins, viaMultivariate Mutual Information (MMI) and Normalized Moreau-Broto Autocorrelation (NMBAC). Then, we feed the 638- dimentional features into an integrated learning model for judging interaction pairs and non-interaction pairs. Furthermore, this integrated model embeds Random Forest in AdaBoost framework and turns weak classifiers into a single strong classifier. Meanwhile, we also employ double fault detection in order to suppress over-adaptation during the training process. Results: To evaluate the performance of our method, we conduct several comprehensive tests for PPIs prediction. On the H. pyloridataset, our method achieves 88.16% accuracy and 87.68% sensitivity, the accuracy of our method is increased by 0.57%. On the S. cerevisiaedataset, our method achieves 95.77% accuracy and 93.36% sensitivity, the accuracy of our method is increased by 0.76%. On the Humandataset, our method achieves 98.16% accuracy and 96.80% sensitivity, the accuracy of our method is increased by 0.6%. Experiments show that our method achieves better results than other outstanding methods for sequence-based PPIs prediction. The datasets and codes are available at https://github.com/guofei-tju/RF-Ada-DF.git.

scholarly journals Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chun-Song Yang ◽  
Kasey Jividen ◽  
Teddy Kamata ◽  
Natalia Dworak ◽  
Luke Oostdyk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Prostate Cancer Cells ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Complex Assembly ◽  
Adp Ribosylation ◽  
Signaling Axis ◽  
Regulate Protein ◽  
Protein Complex Assembly

AbstractAndrogen signaling through the androgen receptor (AR) directs gene expression in both normal and prostate cancer cells. Androgen regulates multiple aspects of the AR life cycle, including its localization and post-translational modification, but understanding how modifications are read and integrated with AR activity has been difficult. Here, we show that ADP-ribosylation regulates AR through a nuclear pathway mediated by Parp7. We show that Parp7 mono-ADP-ribosylates agonist-bound AR, and that ADP-ribosyl-cysteines within the N-terminal domain mediate recruitment of the E3 ligase Dtx3L/Parp9. Molecular recognition of ADP-ribosyl-cysteine is provided by tandem macrodomains in Parp9, and Dtx3L/Parp9 modulates expression of a subset of AR-regulated genes. Parp7, ADP-ribosylation of AR, and AR-Dtx3L/Parp9 complex assembly are inhibited by Olaparib, a compound used clinically to inhibit poly-ADP-ribosyltransferases Parp1/2. Our study reveals the components of an androgen signaling axis that uses a writer and reader of ADP-ribosylation to regulate protein-protein interactions and AR activity.

scholarly journals The Protein Interactome of Glycolysis in Escherichia coli

Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 16
Author(s):  
Shomeek Chowdhury ◽  
Stephen Hepper ◽  
Mudassir K. Lodi ◽  
Milton H. Saier ◽  
Peter Uetz
Keyword(s):  
Escherichia Coli ◽  
Protein Interactions ◽  
Allosteric Regulation ◽  
Glycolytic Enzymes ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Interacting Protein ◽  
E Coli ◽  
Protein Interactome ◽  
The Impact

Glycolysis is regulated by numerous mechanisms including allosteric regulation, post-translational modification or protein-protein interactions (PPI). While glycolytic enzymes have been found to interact with hundreds of proteins, the impact of only some of these PPIs on glycolysis is well understood. Here we investigate which of these interactions may affect glycolysis in E. coli and possibly across numerous other bacteria, based on the stoichiometry of interacting protein pairs (from proteomic studies) and their conservation across bacteria. We present a list of 339 protein-protein interactions involving glycolytic enzymes but predict that ~70% of glycolytic interactors are not present in adequate amounts to have a significant impact on glycolysis. Finally, we identify a conserved but uncharacterized subset of interactions that are likely to affect glycolysis and deserve further study.

scholarly journals Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 791
Author(s):  
Qi Liu ◽  
Bayonle Aminu ◽  
Olivia Roscow ◽  
Wei Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Therapeutic Agents ◽  
Biological Processes ◽  
Post Translational Modification ◽  
E3 Ligases ◽  
Tumor Microenvironments ◽  
Cellular Immune ◽  
Ubiquitin Conjugating Enzymes ◽  
Cellular Components

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.

scholarly journals Interaction of Temporin-L Analogues with the E. coli FtsZ Protein

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 704
Author(s):  
Angela Di Somma ◽  
Carolina Canè ◽  
Antonio Moretta ◽  
Angela Duilio
Keyword(s):  
Protein Interactions ◽  
Bacterial Infections ◽  
Antibacterial Properties ◽  
Bacterial Cell Division ◽  
Structural Determinants ◽  
E Coli ◽  
Functional Studies ◽  
Division Process ◽  
Z Ring ◽  
Peptide Complexes

The research of new therapeutic agents to fight bacterial infections has recently focused on the investigation of antimicrobial peptides (AMPs), the most common weapon that all organisms produce to prevent invasion by external pathogens. Among AMPs, the amphibian Temporins constitute a well-known family with high antibacterial properties against Gram-positive and Gram-negative bacteria. In particular, Temporin-L was shown to affect bacterial cell division by inhibiting FtsZ, a tubulin-like protein involved in the crucial step of Z-ring formation at the beginning of the division process. As FtsZ represents a leading target for new antibacterial compounds, in this paper we investigated in detail the interaction of Temporin L with Escherichia coli FtsZ and designed two TL analogues in an attempt to increase peptide-protein interactions and to better understand the structural determinants leading to FtsZ inhibition. The results demonstrated that the TL analogues improved their binding to FtsZ, originating stable protein-peptide complexes. Functional studies showed that both peptides were endowed with a high capability of inhibiting both the enzymatic and polymerization activities of the protein. Moreover, the TL analogues were able to inhibit bacterial growth at low micromolar concentrations. These observations may open up the way to the development of novel peptide or peptidomimetic drugs tailored to bind FtsZ, hampering a crucial process of bacterial life that might be proposed for future pharmaceutical applications.

scholarly journals Cascading from SARS-CoV-2 to Parkinson’s Disease through Protein-Protein Interactions

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 897
Author(s):  
Ernesto Estrada
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Interactions ◽  
Molecular Level ◽  
Direct Consequence ◽  
Viral Proteins ◽  
Clinical Findings ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Bioinformatic Tools

Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson’s disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD, some hypotheses have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients, in general, and for the PD cases reported, in particular. Given the importance of this potential connection, we present here a molecular-level mechanistic hypothesis that explains well these findings and will serve to explore the potential CNS damage in COVID-19 patients. The model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Our hypothesis is supported by finding 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. The molecular-level mechanistic hypothesis presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.

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